Abstract

Androgen receptor (AR) is a ligand-activated transcription factor that is the main target for treatment of non-organ-confined prostate cancer (CaP). Failure of life-prolonging AR-targeting androgen deprivation therapy is due to flexibility in steroidogenic pathways that control intracrine androgen levels and variability in the AR transcriptional output. Androgen biosynthesis enzymes, androgen transporters and AR-associated coregulators are attractive novel CaP treatment targets. These proteins, however, are characterized by multiple transcript variants and isoforms, are subject to genomic alterations, and are differentially expressed among CaPs. Determining their therapeutic potential requires evaluation of extensive, diverse datasets that are dispersed over multiple databases, websites and literature reports. Mining and integrating these datasets are cumbersome, time-consuming tasks and provide only snapshots of relevant information. To overcome this impediment to effective, efficient study of AR and potential drug targets, we developed the Regulators of Androgen Action Resource (RAAR), a non-redundant, curated and user-friendly searchable web interface. RAAR centralizes information on gene function, clinical relevance, and resources for 55 genes that encode proteins involved in biosynthesis, metabolism and transport of androgens and for 274 AR-associated coregulator genes. Data in RAAR are organized in two levels: (i) Information pertaining to production of androgens is contained in a ‘pre-receptor level’ database, and coregulator gene information is provided in a ‘post-receptor level’ database, and (ii) an ‘other resources’ database contains links to additional databases that are complementary to and useful to pursue further the information provided in RAAR. For each of its 329 entries, RAAR provides access to more than 20 well-curated publicly available databases, and thus, access to thousands of data points. Hyperlinks provide direct access to gene-specific entries in the respective database(s). RAAR is a novel, freely available resource that provides fast, reliable and easy access to integrated information that is needed to develop alternative CaP therapies.Database URL: http://www.lerner.ccf.org/cancerbio/heemers/RAAR/search/

Highlights

  • The androgen receptor (AR) is a member of the ligandactivated family of nuclear receptors

  • AR binds to androgen response elements (AREs) where it assembles the transcriptional complexes to control the expression of target genes [1, 2]

  • Other adaptations affect the pre-receptor level of AR signal transduction, which entails the production of the bioactive ligand that activates AR, dihydrotestosterone (DHT), while still others affect the post-receptor level, which consists of a variety of molecular mechanisms by which activated AR to induce changes in target gene expression [9, 11]

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Summary

Introduction

The androgen receptor (AR) is a member of the ligandactivated family of nuclear receptors. RAAR integrates access to wellestablished and well-curated databases that provide userfriendly and ready-to-use comprehensive information on gene function, clinical relevance, and technical details for research resources for each RAAR entry.

Results
Conclusion

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